Molecular analysis of a gene affecting social cognition

描述(申请人提供)：自闭症患者和9%的正常男性患者存在社会认知缺陷。一种名为EFHC2的X连锁基因已经在特纳综合征女性中被定位，其中30%的女性表现出自闭症样缺陷。对EFHC2的功能一无所知。我们将首先解析EFHC2的等位基因、空间和时间表达模式。我们的下一个目标是确定EFHC2的正常性质。我们将解决EFHC2在神经元中的亚细胞定位，并测定钙结合。我们的最终目标是确定EFHC2的哪一种自然变异具有功能性后果。我们将通过基因分型和分析Turner综合征患者的关联性，对EFHC2基因座进行测序，并缩小功能性SNPs的范围。我们将评估EFHC2变异对表达或钙结合的分子后果。我们的最终目标是评估神经递质的释放是否受到与恐惧识别相关的EFHC2基因变异的影响。对影响社会认知的基因进行功能分析，有助于理解自闭症，揭示正常的社会生理学，并开发剖析复杂特征的方法。

DESCRIPTION (provided by applicant): Deficits in social cognition are present in autism and 9% of otherwise normal males. An X-linked gene, EFHC2, has been mapped in women with Turner Syndrome, 30% of whom show autism-like deficits. Nothing is known about the function of EFHC2. We will first resolve the allelic, spatial, and temporal expression pattern of EFHC2. Our next aim will determine the normal properties of EFHC2. We will resolve the subcellular location of EFHC2 in neurons and assay Ca2+ binding. Our final aim is to determine which natural variation in EFHC2 has functional consequences. We will sequence the EFHC2 locus and narrow down functional SNPs by genotyping and analyzing association in Turner Syndrome patients. We will assess the molecular consequences of EFHC2 variation on expression or calcium binding. Our ultimate goals would be to evaluate whether neurotransmitter release is influenced by the genetic variation in EFHC2 associated with fear recognition. Functional analysis of a gene influencing social cognition could contribute to understanding autism, revealing normal social physiology, and developing methods for the dissection of complex traits.